PROJECT SUMMARY/ABSTRACT?Cancer Biology Program The overarching goal of the Cancer Biology Program (CBP) is to explore and understand the cell biology of cancer. In working toward this goal, we lead integrated and transdisciplinary efforts to define pathways related to cancer, identify driver mutations and genetic anomalies as new leads for therapeutic targeting, and explore and exploit anti-cancer mechanisms as routes to translation into clinical trials. The Program is led by Martine F. Roussel, PhD, an internationally recognized expert on the regulation of the G1 phase of the cell cycle and proliferation as it relates to pediatric cancers, and Douglas R. Green, PhD, a world-renowned scientist studying the mechanisms that dictate cell death and survival, including apoptosis, necroptosis, autophagy, and metabolism in cancer and the immune system. They work together to translate discovery research to the clinic by stimulating scientific exchanges, collaborations between our members and members of the other Cancer Center Programs, and the active participation of our membership in meetings. CBP members are organized into four programmatic working groups formulated to address unmet needs in the understanding of pediatric cancer biology: Cancer Cell Signaling Networks and Therapeutics, Cell Death, Cell Stress Repair and Metabolism, Tumor Microenvironment and Immunology, and Genome Structure and Function. CBP has 29 members, including 21 Full Members and 8 Associate Members (junior mentored) from 12 Departments. During the current funding period, research in CBP has resulted in 570 primary research publications, of which 23.9% were inter-programmatic, demonstrating the key role of CBP members in supporting disease-focused research through basic discovery, 12.8% were intra-programmatic, and 76.5% were inter-institutional (with other NCI-designated Cancer Centers). 38% of our research publications were in journals with impact factor >10. This work includes the genomic landscape of all pediatric cancers through the development of the Pediatric Cancer Genome Project that unraveled the critical role of epigenetic regulators in cancer, fundamental insights into mechanisms of cell death and cell survival, and elucidation of innate and adaptive immune functions impacting our understanding of anti-cancer immunity. CBP members have a total of $6M in peer-reviewed funding. CBP members have made a number of basic science discoveries have been translated into the clinic, greatly facilitated by interactions with other SJCCC Programs. This includes FDA-approval of CDK4/6 inhibitors currently in clinical trials for treatment of breast cancer and the repurposing of gemcitabine and pemetrexed for the treatment of high risk medulloblastoma in collaboration with members of the NBTP. Because SJCCC is focused solely on pediatric cancer, investigators study and develop trials for a diverse spectrum of pediatric cancers utilizing a full array of therapeutic approaches. Consequently, our working groups are broad by design to maximize opportunities for collaborative translation and to position the program well to address opportunities and priorities as they emerge.